<2023-04-25 Tue> David biweekly meeting

Mechanical role of Type I myosin in CME theory project

recent progress

  • systematically discussed model parameters with Matt and Ross to classify each into categories:
    • fixed in "baseline" model
      • myosin diffusion rate
      • myosin step size force sensitivity (slip-through has not been detected experimentally)
    • varied for focus of modeling "experiments"
      • unloaded myosin-actin unbinding rate
      • force sensitivity of myosin-actin unbinding rate
      • resistance to bud internalization
      • myosin copy number
    • fixed for now, but flagged to revisit in future investigations
      • myosin-actin binding rate (set by phosphate release rate in ATPase cycle)
      • myosin-membrane binding kinetics and force sensitivity
      • direction-dependent force sensitivity of actin-myosin unbinding
  • decided on sticking with the older version of cytosim for this project because I don't know how long it will take to make the type I myosin in Matt's new version
  • successfully implemented diffusion of myosins model (I used to have them fixed)
    • myosin z-positions over time

      2023-04-25_11-41-34_20230420_membrane_myosin_zpos-vs-time_all.png
    • myosin x-y positions projected over all simulation time

      2023-04-25_11-42-35_20230420_membrane_myosin_xypos_all.png
    • super-resolution data can help for fitting diffusion coefficient (Mund et al. 2018)

      2023-04-25_11-46-22_2023_04_25_Selection_01.png
  • found a new quirk in the model: myosin appears to be displaced upon binding actin (diffusion rate of myosin [light blue dots] is 0 in this example)

    2023-04-25_11-50-01_2023_04_25_Selection_02.png
    • this can also be seen in the x-y plots above
  • more detailed collaborative notes here

next steps

  • troubleshoot actin-bound myosin movement in simulations
    • run a simulation where every single simulation step is output
  • validate force-insensitivity of myosin step size
  • validate forces exerted on myosin-actin bonds are within reasonable range
  • validate forces exerted on myosin-membrane bonds are within reasonable range
  • adjust parameters for baseline simulation
  • set up new simulation parameters sweeps once baseline model is finished
  • develop analysis strategy for characterizing differences in actin organization and how that might explain differences in CME success due to myosin properties

Date: \today

Author: Max Ferrin

Email: ferrinm@berkeley.edu

Created: 2023-04-25 Tue 12:04

Validate